The goal of this project is the development of new and more effective treatment modalities for patients harboring central nervous system tumors. Using animal models, four different lines of investigation are in progress. (1) Brain Tumor Chemotherapy: Using the mouse Ependymoblastoma model and the rat Glioma model a series of chemotherapeutic agents are being tested for their ability to increase survival and to inhibit DNA synthesis in tumors. The efficacy of these drugs within the tumor and along the growing edge where the blood-brain barrier may interfere with chemotherapeutic agents is also being tested. The distribution of parenchymally administered drugs in brain tumor and in the neuraxis is being studied and compared to distribution of drug when injected systemically. (2) Cerebral Edema and Intracranial Pressure: The source of cerebral edema surrounding brain tumors will be sought using radioactive markers on the presumption that edema fluid comes from within the tumor and diffuses in the normal brain. The effects of steroids on this fluid and on enzyme activity, specifically lysosomes and ATPase, will be studied and the effect of such agents and radiation therapy on intracranial pressure. (3) New Animal Models: These are being developed for meningeal carcinomatosis, epidural spinal cord compression and cerebral metastases using Walker 256 carcinosarcoma in the rat with instillation of tumor into the subarachnoid space, ventricles, dorsal-cervical vertebral region and via carotid artery. (4) Immunity: Immune mechanisms in the treatment of mouse Ependymoblastoma utilizing concomitant tumor immunity, adoptive transfer and the value of immunization with BCG and C. Parvum are being investigated.